Berberine governs NOTCH3/AKT signaling to enrich lung-resident memory T cells during tuberculosis

• DOI: 10.1371/journal.ppat.1011165
• Publication Date: 2023-03-07T18:31:13Z
• Authors: Isha Pahuja; Kriti Negi; Anjna Kumari; Meetu Agarwal; Suparba Mukhopadhyay; Babu Mathew; Shivam Chaturvedi; Jaswinder Singh M...; Ashima Bhaskar; Ved Prakash Dwivedi
• Keywords: Memory T cell; Permissiveness

Stimulation of naïve T cells during primary infection or vaccination drives the differentiation and expansion effector memory that mediate immediate long-term protection. Despite self-reliant rescue from infection, BCG vaccination, treatment, is rarely established against Mycobacterium tuberculosis ( M . tb ) resulting in recurrent (TB). Here, we show berberine (BBR) enhances innate defense mechanisms stimulates Th1/Th17 specific (T EM ), central CM tissue-resident RM responses leading to enhanced host protection drug-sensitive drug-resistant TB. Through whole proteome analysis human PBMCs derived PPD + healthy individuals, identify BBR modulated NOTCH3/PTEN/AKT/FOXO1 pathway as mechanism elevated CD4 cells. Moreover, BBR-induced glycolysis resulted functions superior murine This regulation cell by remarkably BCG-induced anti-tubercular immunity lowered rate TB recurrence due relapse re-infection. These results thus suggest tuning immunological a feasible approach augment resistance unveil potential adjunct immunotherapeutic immunoprophylactic